Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study (preprint)

Background: Hong Kong contained COVID-19 for two years, but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults [≥]65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic.

Estimating the transmission dynamics of Omicron in Beijing, November to December 2022 (preprint)

We tracked the effective reproduction number Rt of Omicron BF.7 in Beijing in November - December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on November 1-11 (when the zero-covid interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on December 10-14 and self-reported to have been previously test-positive. After the announcement of "20 measures", we estimated that Rt increased to 3.42 (95% CrI: 2.79 - 4.17) on November 18. Infection incidence peaked on December 10, and the cumulative infection attack rate was 42.5% (95% CrI: 20.3 - 63.9) on December 14. Surveillance programmes should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.

Characterizing human collective behaviours of COVID-19 in Hong Kong (preprint)

People are likely to engage in collective behaviour online during extreme events, such as the COVID-19 crisis, to express their awareness, actions and concerns. Hong Kong has implemented stringent public health and social measures (PHSMs) to curb COVID-19 epidemic waves since the first COVID-19 case was confirmed on 22 January 2020. People are likely to engage in collective behaviour online during extreme events, such as the COVID-19 crisis, to express their awareness, actions and concerns. Here, we offer a framework to evaluate interactions among individuals emotions, perception, and online behaviours in Hong Kong during the first two waves (February to June 2020) and found a strong correlation between online behaviours of Google search and the real-time reproduction numbers. To validate the model output of risk perception, we conducted 10 rounds of cross-sectional telephone surveys from February 1 through June 20 in 2020 to quantify risk perception levels over time. Compared with the survey results, the estimates of the risk perception of individuals using our network-based mechanistic model capture 80% of the trend of people risk perception (individuals who worried about being infected) during the studied period. We may need to reinvigorate the public by engaging people as part of the solution to live their lives with reduced risk.

Predictive efficacies of vaccine dose fractionation using neutralizing antibody levels (preprint)

Background With the emergence of SARS-CoV-2 variants that eluded immunity from vaccines and prior infections, vaccine shortages and their effectiveness pose unprecedented challenges for governments to expand booster vaccination programs. Fractionation of vaccine doses might be an effective strategy to help society to face these challenges, which may have comparable efficacies in contrast with the standard doses. Methods In this study, we analyzed the relationship between in-vitro neutralization levels and the observed efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines using data from 13 studies from vaccination and convalescent cohorts. We further projected efficacies for fractional doses based on 51 studies included in our systematic review. Results By comparing with the convalescent level, vaccine efficacy increases from 8.8% (95% CI: 1.4%, 16.1%) to 71.8% (95% CI: 63.0%, 80.7%) against asymptomatic infection, and from 33.6% (95% CI: 23.6%, 43.6%) to 98.6% (95% CI: 97.6%, 99.7%) against symptomatic infection, respectively, along with the mean neutralization level from 0.1 to 10 folds of convalescent level. And mRNA vaccines provide the strongest protection, and decrease slowly for fractional dosing between 50% and 100% dosage. Conclusions Our results are consistent with studies for immune protection from COVID-19 infection. Based on our study, we expect that fractional dose vaccination could provide a partial immunity for SARS-CoV-2 virus. Fractional doses of vaccines could be a viable vaccination strategy compared to full-dose vaccination and deserves further exploration. Key points We analyzed the relationship between neutralization levels and efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines from convalescent cohorts. Fractional doses of vaccines could be a viable strategy compared to full-dose vaccination and deserves further exploration.

The effectiveness of conversational AI services on Covid-19 vaccine confidence and acceptance in Thailand, Hong Kong, and Singapore (preprint)

During the COVID-19 pandemic, the emergence of the infodemic and vaccine hesitancy posed a significant challenge to adequate vaccine uptake. In response, conversational AI services such as chatbots have become an increasingly popular tool in the field of health service delivery and communication to increase individuals’ health literacy and vaccination intention. However, few studies have performed a rigorous evaluation of the effectiveness of chatbots as a means of improving vaccine confidence and acceptance. In Thailand, Hong Kong, and Singapore, from February 11th to June 30th, 2022, we conducted multisite randomised controlled trials (RCT) on 2,045 adults with unvaccinated dependent family members who were vulnerable (i.e., seniors) and had been refusing/delaying vaccination, or newly eligible for vaccines (i.e., children). After a week of using multilingual COVID-19 vaccine chatbots, the differences in vaccine confidence - measured by the Vaccine Confidence Index - and acceptance were compared between the intervention and control groups. Factors of vaccine confidence and acceptance were explored. Compared to non-users, a smaller proportion of chatbot users reported a decrease of confidence in vaccine effectiveness in the Thailand child group [Intervention: 4·3% vs. Control: 17%, P = 0·023] and Hong Kong child group [10% vs. 26%, P = 0·034], and of vaccine effectiveness in reducing severe conditions in the Thailand senior group [12% vs. 21%, P = 0·024]. There was no significant change in vaccine confidence or acceptance in the Singapore child group and Hong Kong senior group. Employing the RE-AIM framework, process evaluation indicated strong acceptance and implementation support for vaccine chatbots from stakeholders, with high levels of sustainability and scalability. This study was the first multisite, parallel RCT on vaccine chatbots and reported mixed success in improving vaccine confidence and acceptance among highly hesitant Asian subpopulations. Deploying chatbots as a complement to existing vaccination strategies could identify users’ main concerns for rejecting/delaying vaccination and facilitate a targeted communication and engagement strategy. Trial registration: NCT05424952

An observational study on imported COVID-19 cases in Hong Kong during mandatory on-arrival hotel quarantine (preprint)

Background: Hong Kong has enforced stringent travel restrictions particularly for inbound travellers since the emergence of SARS-CoV-2. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: We conducted a retrospective cohort study to summarise the characteristics of cases classified as imported cases that were detected on or soon after arrival into Hong Kong from 13 November 2020 through to 31 January 2022, when all arriving persons were required to quarantine in a hotel or a designated quarantine facility. We analysed individual demographics, and clinical information including symptoms and disease severity, virus variants, and Ct values. Results: There were 2269 imported COVID-19 cases aged 0-85 years identified in Hong Kong. Almost half (48.6%) of the imported cases were detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than cases infected with the ancestral strain and other variants (12 days; p<0.001) while lower Ct values at isolation were observed in cases infected with Omicron than the ancestral strain or other variants. No Omicron cases were detected beyond 14 days after arrival, and the cases (n=58, 2.6%) detected after 14 days of quarantine more frequently presented without symptoms at isolation and had a higher RT-PCR Ct-value during isolation. At least some of these cases were post-arrival infections. Conclusions: Testing inbound travellers at arrival and during on-arrival quarantine can detect imported cases early although it may not be sufficient to prevent all introductions of COVID-19 into the community. Public health measures should be adjusted in responses to the emergence of new variants of SARS-CoV-2 based on the epidemiologic evidence from continuous surveillance.

Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19 (preprint)

The generation time distribution, reflecting the time between successive infections in transmission chains, is a key epidemiological parameter for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. We investigated incubation period and serial interval distributions in data on 2989 confirmed cases in China in January-February 2020, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. We identified substantial reductions over time in the serial interval and generation time distributions. Our proposed method provides more reliable estimation of the temporal variation in the generation time distribution, improving assessment of transmission dynamics.

Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19 (preprint)

Background The generation time distribution, reflecting the time between successive infections in transmission chains, is one of the fundamental epidemiological parameters for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution, reflecting the time between illness onsets of infector and infectee. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. Methods We analyzed data on observed incubation period and serial interval distributions in China, during January and February 2020, under different sampling approaches, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. Results We analyzed data on a total of 2989 confirmed cases for COVID-19 during January 1 to February 29, 2020 in Mainland China. During the study period, the empirical forward serial interval decreased from a mean of 8.90 days to 2.68 days. The estimated mean backward incubation period of infectors increased from 3.77 days to 9.61 days, and the mean forward incubation period of infectees also increased from 5.39 days to 7.21 days. The estimated mean forward generation time decreased from 7.27 days (95% confidence interval: 6.42, 8.07) to 4.21 days (95% confidence interval: 3.70, 4.74) days by January 29. We used simulations to examine the sensitivity of our modelling approach to a number of assumptions and alternative dynamics. Conclusions The proposed method can provide more reliable estimation of the temporal variation in the generation time distribution, enabling proper assessment of transmission dynamics.

Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir against mortality, hospitalization, and in-hospital outcomes among community-dwelling, ambulatory COVID-19 patients during the BA.2.2 wave in Hong Kong: an observational study (preprint)

Background Evidence evaluating real-world effectiveness of oral antivirals against Omicron variants is lacking. Methods An unselected, territory-wide cohort of all initially non-hospitalized patients with an officially registered diagnosis of SARS-CoV-2 infection between 26th February and 3rd May 2022 during the Omicron BA.2.2 wave in Hong Kong, was identified. We undertook a retrospective cohort design as primary analysis, and case-control design as sensitivity analysis. Outpatient oral antiviral users were matched with controls using 1:10 propensity-score matching. Study outcomes were mortality, COVID-19-related hospitalization, composite outcome of in-hospital disease progression (in-hospital mortality, invasive mechanical ventilation, or intensive care unit admission) and its individual outcomes. Hazard ratios (HR) were estimated by Cox regression, and odds ratios in oral antiviral users compared with non-users by logistic regression. Subgroup analyses evaluated the associations by vaccination status and age. Findings Among 1,072,004 non-hospitalized COVID-19 patients, 5,257 and 5,663 were initiated molnupiravir and nirmatrelvir/ritonavir in the community setting with a median follow-up of 42 and 38 days, respectively. Molnupiravir use was associated with lower risks of mortality (HR=0·61, 95%CI=0·46-0·82, p<0·001) and in-hospital composite outcome (HR=0·64, 95%CI=0·50-0·83, p<0·001) than non-use, while that of hospitalization was comparable to controls (HR=1·06, 95%CI=0·97-1·16, p=0·191). Nirmatrelvir/ritonavir use was associated with lower risks of mortality (HR=0·25, 95%CI=0·13-0·47, p<0·001), hospitalization (HR=0·69, 95%CI=0·60-0·79, p<0·001), and in-hospital outcome (HR=0·47, 95%CI=0·31-0·71, p<0·001) than non-use. Similar protective effects of nirmatrelvir/ritonavir were observed across vaccination status (fully vaccinated versus otherwise) and age (dichotomized at 65 years), whereas those for molnupiravir were less consistent. Findings from case-control analysis broadly confirmed those of primary analysis. Interpretation Amid the Omicron BA.2.2 wave, early initiation of oral antivirals among non-institutionalised COVID-19 patients was associated with reduced risks of mortality and in-hospital outcomes. Nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir. Funding Health and Medical Research Fund, Food and Health Bureau Research in context Evidence before this study Oral antivirals have been initiating in non-hospitalized COVID-19 patients to lower their risks of hospitalization and death, and hence to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 25 May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the outpatient use of molnupiravir and nirmatrelvir/ritonavir are MOVe-OUT and EPIC-HR trials, respectively. Both have been conducted among unvaccinated, non-hospitalized patients with mild-to-moderate COVID-19 who are at risk of progression to severe disease, during a pandemic wave of SARS-CoV-2 Delta variant. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Considering the real-world evaluation of the two oral antivirals against the currently circulating Omicron variant, only one single-center, retrospective review of solid organ transplant recipients with COVID-19 has been conducted; yet their results are unlikely generalizable to other populations given its specific patient group and small sample size. Real-world effectiveness of oral antivirals is urgently needed to inform their clinical use in COVID-19 patients, considering their vaccination status and the variant of concern. Added value of this study To the best of our knowledge, this is one of the first real-world studies exploring the clinical use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. A territory-wide, retrospective cohort study was conducted to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in community-dwelling COVID-19 patients. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset was associated with significant reduction of all-cause mortality risk by 39% and 75%, respectively, compared to not using any oral antivirals. Nirmatrelvir/ritonavir use was also associated with a reduced risk of COVID-19-related hospitalization by 31%, which was consistently observed across age and vaccination status. In terms of disease progression, both oral antivirals were effective in lowering the risk of in-hospital death, which was again more substantial with nirmatrelvir/ritonavir than molnupiravir. Intriguingly, the need for invasive ventilation might be reduced among molnupiravir users compared to matched controls. Implications of all the available evidence Based on relative efficacy, our findings give support to current guidelines prioritizing nirmatrelvir/ritonavir use over molnupiravir in community-dwelling COVID-19 patients who are at high risk of hospitalization or progression to severe disease, should the former be accessible and clinically appropriate. Amid a pandemic wave of the Omicron variant, real-world effectiveness of oral antivirals in reducing the mortality risk of community-dwelling COVID-19 patients has been demonstrated in this study consisting mostly of the elderly and those who had not been fully vaccinated, extending beyond the evidence demonstrated in clinical trials among those of the Delta variant and who were at risk of severe COVID-19 from being overweight/obese. Several clinical trials (namely RECOVERY and PANORAMIC) and observational studies of the two oral antivirals are ongoing, and further research is needed to confirm our results in other patient populations and healthcare settings.

Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir among COVID-19 inpatients during Hong Kong's Omicron BA.2 wave: an observational study (preprint)

Background Real-world evidence on the effectiveness of oral antivirals in mild-to-moderate COVID-19 patients is urgently needed. This retrospective cohort study aims to evaluate the clinical and virologic outcomes associated with molnupiravir and nirmatrelvir/ritonavir use in COVID-19 patients during a pandemic wave dominated by the Omicron BA.2 variant. Methods We analyzed data from a territory-wide retrospective cohort of hospitalized patients with confirmed diagnosis of SARS-CoV-2 infection from 26th February 2022 to 26th April 2022 in Hong Kong. Oral antiviral users were matched with controls using propensity-score matching in a ratio of 1:4. Study outcomes were a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], or intensive care unit admission) and their individual outcomes, and lower viral load of cycle threshold (Ct) value [≥]30 cycles. Hazard ratios (HR) of event outcomes were estimated using Cox regression models. Results Among 40,776 hospitalized patients with SARS-CoV-2 infection over a mean follow-up of 41.3 days with 925,713 person-days, 2,359 and 1,000 patients not initially requiring oxygen therapy were initiated with molnupiravir and nirmatrelvir/ritonavir, respectively. The crude incidence rates of all-cause mortality and IMV were 22.24 and 1.06 events per 10,000 person-days among molnupiravir users, 11.04 and 1.75 events per 10,000 person-days among nirmatrelvir/ritonavir users. Oral antiviral use was associated with a significantly lower risk of the composite outcome of disease progression (molnupiravir: HR=0.53, 95%CI=0.46-0.62, p<0.001; nirmatrelvir/ritonavir: HR=0.33, 95%CI=0.24-0.46, p<0.001) than non-use, which was consistently observed for all-cause mortality (molnupiravir: HR=0.55, 95%CI=0.47-0.63, p<0.001; nirmatrelvir/ritonavir: HR=0.32, 95%CI=0.23-0.45, p<0.001). Molnupiravir users had lower risks of IMV (HR=0.31, 95%CI=0.16-0.61, p<0.001). Time to achieving lower viral load was significantly shorter among oral antiviral users than matched controls (molnupiravir: HR=1.21, 95%CI=1.07-1.37, p=0.002; nirmatrelvir/ritonavir: HR=1.25, 95%CI=1.04-1.50, p=0.015). Amongst survivors, nirmatrelvir/ritonavir had shorter length of hospital stay (-0.70 days, 95%CI=-1.37 to -0.04, p=0.039) than matched controls. Head-to-head comparison of molnupiravir and nirmatrelvir/ritonavir reported higher risk of mortality (HR=1.53 95%CI=1.01-2.31, p=0.047) and longer length of hospital stay (0.83 days, 95%CI=0.07-1.58, p=0.032) for molnupiravir users. Conclusions Against Omicron BA.2, initiation of novel oral antiviral treatment in hospitalized patients not requiring any oxygen therapy was associated with lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster.

Epidemiology of infections with SARS-CoV-2 Omicron BA.2 variant in Hong Kong, January-March 2022 (preprint)

Hong Kong reported 12,631 confirmed COVID-19 cases and 213 deaths in the first two years of the pandemic but experienced a major wave predominantly of Omicron BA.2.2 in early 2022 with over 1.1 million reported SARS-CoV-2 infections and more than 7900 deaths. Our data indicated a shorter incubation period, serial interval, and generation time of infections with Omicron than other SARS-CoV-2 variants. Omicron BA.2.2 cases without a complete primary vaccination series appeared to face a similar fatality risk to those infected in earlier waves with the ancestral strain.

Time-varying transmission heterogeneity of SARS and COVID-19 in Hong Kong (preprint)

Transmission heterogeneity is a notable feature of the severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) epidemics, though previous efforts to estimate how heterogeneity changes over time are limited. Using contact tracing data, we compared the epidemiology of SARS and COVID-19 infection in Hong Kong in 2003 and 2020-21 and estimated time-varying transmission heterogeneity (kt) by fitting negative binomial models to offspring distributions generated across variable observation windows. kt fluctuated over time for both COVID-19 and SARS on a continuous scale though SARS exhibited significantly greater (p < 0.001) heterogeneity compared to COVID-19 overall and in-time. For COVID-19, kt declined over time and was significantly associated with increasingly stringent non-pharmaceutical interventions though similar evidence for SARS was inconclusive. Underdetection of sporadic COVID-19 cases led to a moderate overestimation of kt, indicating COVID-19 heterogeneity of could be greater than observed. Time-varying or real-time estimates of transmission heterogeneity could become a critical indicator for epidemic intelligence in the future.

Neutralizing antibody titres to SARS-CoV-2 Omicron variant and wild-type virus in those with past infection or vaccinated or boosted with mRNA BNT162b2 or inactivated CoronaVac vaccines (preprint)

Omicron, a novel SARS-CoV-2 variant has emerged and is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in serum of convalescent or vaccinated individuals to understand potential loss of protection from infection or re-infection. Two doses of BNT162b2 or CoronaVac vaccines provided little 50% plaque reduction neutralization test (PRNT 50 ) antibody immunity against the Omicron variant, even at one-month post vaccination. Booster doses with BNT162b2 in those with two doses of either BNT162b2 or CoronaVac provided acceptable neutralizing immunity against Omicron variant at 1-month post-booster dose. However, three doses of BNT162b2 elicited higher levels of PRNT 50 antibody to Omicron variant suggesting longer duration of protection. Convalescent from SARS-CoV-2 infection did not have protective PRNT 50 antibody levels to Omicron, but a single dose of BNT162b2 vaccine provided protective immunity. Field vaccine-efficacy studies against Omicron variant against different vaccines are urgently needed.

Superspreading of SARS-CoV-2 infections: A Systematic Review and Meta-analysis (preprint)

Superspreading in transmission is a feature of SARS-CoV-2 transmission. We conducted a systematic review and meta-analysis on globally reported dispersion parameters of SARS-CoV-2. The pooled estimate was 0.55 (95% CI: 0.30, 0.79). The study location and method were found to be important drivers for its diversity.

International risk of SARS-CoV-2 Omicron variant importations originating in South Africa (preprint)

Omicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.

Comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India: a modelling study (preprint)

Given constrained vaccine supplies globally, fractionation of vaccine doses may be an effective strategy for reducing disease and healthcare burdens, even with the emergence of COVID-19 variants. Using a multi-scale model that incorporates population-level transmission and individual-level vaccination, we estimate the costs associated with hospitalization, vaccine costs, and the economic benefit of reducing COVID-19 deaths associated with dose-fractionation strategies. Assuming a willingness-to-pay of US$10,517 per averted year of life lost (YLL) and a price of $12 per vaccine, under various transmission scenarios, with effective reproduction numbers ranging from 1.1 to 5.0 and with vaccine efficacy against transmission from 52% to 91%, the optimal vaccination strategy would always involve fractional doses of vaccines. Vaccine dose fractionation is a cost-effective strategy for mitigating the COVID-19 pandemic and could save a large number of lives, even after the emergence of variants with higher transmissibility.

Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmissibility (preprint)

Many locations around the world have used real-time estimates of the time-varying effective reproductive number (\({R}_{t}\)) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of \({R}_{t}\) are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the incubation period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by cycle threshold values) and estimates of \({R}_{t}\) based on case counts. We demonstrate that cycle threshold values could be used to improve real-time \({R}_{t}\) estimation, enabling more timely tracking of epidemic dynamics.

Transmission dynamics and epidemiological characteristics of Delta variant infections in China (preprint)

BackgroundThe Delta variant of SARS-CoV-2 has become predominant globally. We evaluated the transmission dynamics and epidemiological characteristics of the Delta variant in an outbreak in southern China. MethodsData on confirmed cases and their close contacts were retrospectively collected from the outbreak that occurred in Guangdong, China in May-June 2021. Key epidemiological parameters, temporal trend of viral loads and secondary attack rates were estimated and compared between the Delta variant and the wild-type SARS-CoV-2 virus. We also evaluated the association of vaccination with viral load and transmission. ResultsWe identified 167 patients infected with the Delta variant in the Guangdong outbreak. The mean estimates of the latent period and the incubation period were 4.0 days and 5.8 days, respectively. A relatively higher viral load was observed in Delta cases than in wild-type infections. The secondary attack rate among close contacts of Delta cases was 1.4%, and 73.9% (95% confidence interval: 67.2%, 81.3%) of the transmissions occurred before onset. Index cases without vaccination (OR: 2.84, 95% confidence interval: 1.19, 8.45) or with one dose of vaccination (OR: 6.02, 95% confidence interval: 2.45, 18.16) were more likely to transmit infection to their contacts than those who had received 2 doses of vaccination. DiscussionPatients infected with the Delta variant had more rapid symptom onset. The shorter and time-varying serial interval should be accounted in estimation of reproductive numbers. The higher viral load and higher risk of pre-symptomatic transmission indicated the challenges in control of infections with the Delta variant.

International risk of the new variant COVID-19 importations originating in the United Kingdom (preprint)

A fast-spreading SARS-CoV-2 variant identified in the United Kingdom in December 2020 has raised international alarm. We estimate that, in all 15 countries analyzed, there is at least a 50% chance the variant was imported by travelers from the United Kingdom by December 7th.